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Selected AbstractsLong-Term Tolerability of Sumatriptan Nasal Spray in Adolescent Patients With MigraineHEADACHE, Issue 10 2004Shankar Natarajan MD Objective.,This 1-year, open-label, multicenter study was designed to assess the long-term tolerability and efficacy of sumatriptan nasal spray 20 mg in adolescent patients with migraine. Methods.,A prospective, multicenter, open-label study was conducted in patients aged 12 to 17 years who were allowed to treat an unlimited number of migraines at severe, moderate, or mild pain intensity with sumatriptan nasal spray for up to 1 year. All patients started the study at the 20-mg dose of sumatriptan nasal spray. Dose could be adjusted downward to 5 mg at the discretion of the investigator to optimize therapy. Results.,A total of 484 adolescent migraineurs treated 4676 migraines with sumatriptan nasal spray 20 mg (3593 during the first 6 months and 1083 during the second 6 months). A total of 3940 migraines and 699 migraines were treated with one and two 20-mg doses of sumatriptan nasal spray, respectively. Only 10 patients (treating 42 migraines) took the 5-mg dose of sumatriptan nasal spray. The overall percentage of migraines treated with either one 20-mg dose or one, two, or three 20-mg doses with at least 1 drug-related adverse event was 19%. The most common specific drug-related adverse event was unpleasant taste, reported in 17% of migraines. No other single drug-related adverse event was reported in more than 1% of migraines over the 1-year treatment period. When unpleasant taste was excluded from the adverse-event tabulations, the percentages of migraines with at least 1 drug-related adverse event after one or one, two, or three 20-mg doses declined to 4% and 3%, respectively. No patient experienced any drug-related changes in 12-lead ECGs, vital signs, or nasal assessments; and no clinically meaningful changes in clinical laboratory values were observed. Across all migraines with evaluable efficacy data (n = 4334), headache relief was reported in 43% of migraines at 1 hour and in 59% at 2 hours after dosing with sumatriptan nasal spray 20 mg. Of the 2561 migraines with headache relief 2 hours postdose, headache recurrence was reported within 24 hours of initial dosing in 7% of migraines. None of the efficacy or tolerability results varied as a function of time in the study (ie, first 6 months vs. second 6 months). Conclusion.,Sumatriptan nasal spray 20 mg is generally well tolerated and may be beneficial during long-term use by adolescent migraineurs ages 12 to 17 years. [source] Medical demography and intergenerational inequalities in general practitioners' earningsHEALTH ECONOMICS, Issue 9 2008B. Dormont Abstract This article examines the link between restrictions on the number of physicians and general practitioners' (GPs) earnings. Using a representative panel of 6016 French self-employed GPs over the years 1983,2004, we estimate an earnings function to identify experience, time and cohort effects. The estimated gap in earnings between ,good' and ,bad' cohorts can be as large as 25%. GPs who began their practices during the eighties have the lowest permanent earnings: they belong to the large cohorts of the baby-boom and face the consequences of an unlimited number of places in medical schools. Conversely, the decrease in the number of places in medical schools led to an increase in permanent earnings of GPs who began their practices in the mid-nineties. A stochastic dominance analysis shows that unobserved heterogeneity does not compensate for average differences in earnings between cohorts. These findings suggest that the first years of practice are decisive for a GP. If competition between physicians is too intense at the beginning of their careers, they will suffer from permanently lower earnings. To conclude, our results show that the policies aimed at reducing the number of medical students succeeded in buoying up physicians' permanent earnings. Copyright © 2008 John Wiley & Sons, Ltd. [source] Concrete Geometry: Playing with BlocksINTERNATIONAL JOURNAL OF ART & DESIGN EDUCATION, Issue 1 2010Andreas Luescher This article describes a design/build exercise conducted in an Architectural Materials and Methods class to achieve three interrelated objectives: (1) to apply physically the semester's theoretical focus on the constituent process and languages of architecture investigations, (2) to capitalise on the physical and aesthetic properties of concrete masonry to explore fabrication and detailing in the design process, and (3) to examine preconceptions about solo work and team work in architectural education and practice. What makes this project unique among other design/build projects is its emphasis on Concrete Masonry Units (known as CMU in the USA) and their visual, tactile and functional properties. The junior and senior students were allowed three building elements: an 8, cube of space, an unlimited number of concrete blocks, and the visual ecology of a site. The structural vocabulary that Frank Lloyd Wright developed consisted of a three-dimensional field of lines through which the solid elements of the building were located, enabling the voids to be integral to the whole and equally meaningful. Using these elements, students were asked to design/build temporary structures in a field next to the airport hangar on campus. The pedagogical objective was to adopt Wright's creative spirit, as opposed to quoting his architectural language. [source] A thousand and one nova outburstsMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 4 2007Noya Epelstain ABSTRACT A full nova cycle includes mass accretion, thermonuclear runaway resulting in outburst and mass-loss, and finally, decline. Resumed accretion starts a new cycle, leading to another outburst. Multicycle nova evolution models have been calculated over the past twenty years, the number being limited by numerical constraints. Here we present a long-term evolution code that enables a continuous calculation through an unlimited number of nova cycles for an unlimited evolution time, even up to 1.5 × 1010 yr. Starting with two sets of the three independent nova parameters , the white dwarf (WD) mass, the temperature of its isothermal core, and the rate of mass transfer on to it , we have followed the evolution of two models, with initial masses of 1 M, and 0.65 M, through over 1000 and over 3000 cycles, respectively. The accretion rate was assumed constant throughout each calculation: 10,11 M, yr,1 for the 1 M, WD, and 10,9 M, yr,1 for the 0.65 M, one. The initial temperatures were taken to be relatively high: 30 × 106 and 50 × 106 K, respectively, as they are likely to be at the onset of the outburst phase. The results show that although on the short-term consecutive outbursts are almost identical, on the long-term scale the characteristics change. This is mainly due to the changing core temperature, which decreases very similarly to that of a cooling WD for a time, but at a slower rate thereafter. As the WD's mass continually decreases, since both models lose more mass than they accrete, the central pressure decreases accordingly. The outbursts on the massive WD change gradually from fast to moderately fast, and the other characteristics (velocity, abundance ratios, isotopic ratios) change, too. Very slowly, a steady state is reached, where all characteristics, both in quiescence and in outburst, remain almost constant. For the less massive WD accreting at a high rate, outbursts are similar throughout the evolution. [source] Extracting metabolite ions out of a matrix background by combined mass defect, neutral loss and isotope filtrationRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 2 2009Filip Cuyckens Mass defect, neutral loss and isotope filtration techniques were applied to electrospray ionization mass spectrometry (ESI-MS) data obtained for in vivo and in vitro samples of drug metabolism studies. A combination of these post-acquisition processing techniques was shown to be more powerful than the use of one of these tools alone for the detection in complex matrices of metabolites of candidate drugs with a characteristic isotope pattern (e.g. containing bromine, chlorine, or a high proportion of radiolabeled drug (12C/14C)) or characteristic neutral losses. In combination with ,all-in-one' data acquisition this methodology is able to perform software-driven constant neutral loss scanning for an unlimited number of mass differences at any time after analysis. Highly selective MS chromatograms were obtained with excellent correlation with their corresponding radiochromatograms. Copyright © 2009 John Wiley & Sons, Ltd. [source] Physiologically Based Modelling and Prediction of Drug InteractionsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2010Frédéric Y. Bois This article reviews briefly past developments in the area of physiologically based pharmacokinetic (PBPK) modelling of interactions. It also demonstrates a systems biology approach to the question, and the capabilities of new software tools to facilitate that development. Individual Systems Biology Markup Language models of metabolic pathways can now be automatically merged and coupled to a template PBPK pharmacokinetic model, using for example the GNU MCSim software. The global model generated is very efficient and able to simulate the interactions between a theoretically unlimited number of substances. Development time and the number of model parameter increase only linearly with the number of substances considered, even though the number of possible interactions increases exponentially. [source] Application creation for IMS systems through macro-enablers and Web 2.0 technologiesBELL LABS TECHNICAL JOURNAL, Issue 1 2010Anne Y. Lee Rapid creation of an unlimited number of innovative new applications has been a promise of the IP Multimedia Subsystem (IMS) from the beginning. However, over the years, attention has been paid more to the development of the IMS foundation than methods for the IMS services factory,which is as it should be. The time has come to now address applications creation. This paper describes a way to enable carriers, third-party application developers, and the public to quickly produce new applications using IMS building blocks and application frameworks as well as Web 2.0 technologies and support for IMS + Internet applications mashups. IMS building blocks and application frameworks are macro application enablers. © 2010 Alcatel-Lucent. [source] Changes in gene expression and morphology of mouse embryonic stem cells on differentiation into insulin-producing cells in vitro and in vivoDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2009Ortwin Naujok Abstract Background Embryonic stem (ES) cells have the potential to produce unlimited numbers of surrogate insulin-producing cells for cell replacement therapy of type 1 diabetes mellitus. The impact of the in vivo environment on mouse ES cell differentiation towards insulin-producing cells was analysed morphologically after implantation. Methods ES cells differentiated in vitro into insulin-producing cells according to the Lumelsky protocol or a new four-stage differentiation protocol were analysed morphologically before and after implantation for gene expression by in situ reverse transcription polymerase chain reaction and protein expression by immunohistochemistry and ultrastructural analysis. Results In comparison with nestin positive ES cells developed according to the reference protocol, the number of ES cells differentiated with the four-stage protocol increased under in vivo conditions upon morphological analysis. The cells exhibited, in comparison to the in vitro situation, increased gene and protein expression of Pdx1, insulin, islet amyloid polypeptide (IAPP), the GLUT2 glucose transporter and glucokinase, which are functional markers for glucose-induced insulin secretion of pancreatic beta cells. Renal sub-capsular implantation of ES cells with a higher degree of differentiation achieved by in vitro differentiation with a four-stage protocol enabled further significant maturation for the beta-cell-specific markers, insulin and the co-stored IAPP as well as the glucose recognition structures. In contrast, further in vivo differentiation was not achieved with cells differentiated in vitro by the reference protocol. Conclusions A sufficient degree of in vitro differentiation is an essential prerequisite for further substantial maturation in a beta-cell-specific way in vivo, supported by cell-cell contacts and vascularisation. Copyright © 2009 John Wiley & Sons, Ltd. [source] Automated maintenance of embryonic stem cell culturesBIOTECHNOLOGY & BIOENGINEERING, Issue 1 2007Stefanie Terstegge Abstract Embryonic stem cell (ESC) technology provides attractive perspectives for generating unlimited numbers of somatic cells for disease modeling and compound screening. A key prerequisite for these industrial applications are standardized and automated systems suitable for stem cell processing. Here we demonstrate that mouse and human ESC propagated by automated culture maintain their mean specific growth rates, their capacity for multi-germlayer differentiation, and the expression of the pluripotency-associated markers SSEA-1/Oct-4 and Tra-1-60/Tra-1-81/Oct-4, respectively. The feasibility of ESC culture automation may greatly facilitate the use of this versatile cell source for a variety of biomedical applications. Biotechnol. Bioeng. 2007;96: 195,201. © 2006 Wiley Periodicals, Inc. [source] | ||||||||||